Sign Up for Our Cancer Care and Prevention Newsletter

Thanks for signing up!

Therapy for advanced breast cancer is constantly evolving as researchers refine treatments to make them more effective with fewer side effects. Learn about the latest discoveries in breast cancer treatment from renowned medical experts by listening to one of these community forums.

Andrew Schorr:

Everyone joins me in thanking the groups that help get the word out about this event, and they include Magee Women's Hospital, University of Pittsburgh Hillman Cancer Center, National Cancer Caring Center, the American Cancer Society, the Susan G. Komen Foundation, the Oncology Nursing Society, and Gilda's Club.

We're honored to have with us here in Pittsburgh Dr. Stanley Marks of the University of Pittsburgh Hillman Cancer Center. Also with us is Dr. Adam Brufsky of Magee Women's Hospital at the University of Pittsburgh Cancer Institute.

And our third panelist is Lauren Haag. She is an information technology director at Eaton Corporation in Pittsburgh. She is a stage II breast cancer survivor since 2002, and she'll tell us about her own personal journey with breast cancer.

Dr. Marks is deputy director of clinical services for the University of Pittsburgh Medical Center Cancer Centers in the University of Pittsburgh Cancer Institute. He's also chief of the Division of Hematology/Oncology at UPMC Shadyside. He is medical director of Forbes Hospice and a clinical associate professor of medicine at the UP School of Medicine. He'll be giving us a brief overview of current treatments for advanced breast cancer.

Dr. Stanley Marks:

I'm going to give you a brief overview of treatments for metastatic, or stage IV, disease, and then Dr. Brufsky is going to go into a little more detail about specific drugs and agents. First is some good news. Certainly, the mortality from breast cancer has been steadily declining for the past 15 years for a variety of reasons. Early detection, mammography and behavior modification has played some role, but we also have new and better treatments for all stages of disease, including metastatic. And we've made great improvements in supportive care for patients, even with far advanced disease, which means that quality of life is improved in all stages of the disease.

These are five-year survival rates. For DCIS or in situ cancer, the cure rate is almost 100 percent. If you go to stage IV disease, we still have a way to go. The five-year survival [rate] is still 20 percent or less. Some of the things that we'll talk about will significantly improve these survival numbers.

In terms of the treatment for patients with metastatic breast cancer, we divide them into three [goals]. We want to stop the progression of the disease with treatment, hopefully prolong a patient's life, and most important, maintain or improve quality of life.

We basically divide patients into two categories - those who have very limited metastases that are sensitive to hormones, and then patients with more advanced disease who have organ involvement and/or who are not hormone-sensitive.

Hormone therapy for metastatic breast cancer is generally used in women without significant organ involvement whose tumor is sensitive to hormone therapy. This is determined by measuring for estrogen and progesterone receptors on the tumor or on the metastatic site. Hormone therapy is good in both premenopausal and postmenopausal women. The hormonal agents you're probably all familiar with. The first one was tamoxifen [Nolvadex]. The newest group are the aromatase inhibitors - Femara [letrozole], Arimidex [anastrozole] and Aromasin [exemestane], which are basically equivalent in efficacy. Then there's the new category of drugs called the estrogen-receptor down regulators. And Faslodex [Fulvestrant], which is a monthly injection, is a very useful hormone agent as well. Finally, when those agents fail, sometimes we will resort to using progesterone or male hormones or androgens in some cases.

In terms of chemotherapy, we use both single-agent chemotherapy, one drug, as well as sometimes combinations of two or three drugs in certain settings. The chemotherapy agents are divided into categories based upon their mechanism of action. We're going time talking about the taxanes - Taxol [paclitaxel], Taxotere [docetaxel] and Abraxane [nab paclitaxel]. We have a whole host of agents that have different mechanisms of action. When we combine these drugs, we try to combine drugs that have different mechanisms of action and not overlapping side effects, so we don't induce too much toxicity, but at the same time we get a combination effect. In some settings, we will actually use three drugs in combination.

Biologic therapy is a whole new area. Biologic therapy refers to therapy where we utilize one's own natural defenses to fight cancer, and these agents fall into the category of targeted therapy, the new paradigm in cancer therapy. These agents specifically target cancer cells and do not damage normal cells and avoid a lot of the toxicities.

A whole host of targeted agents are available, as well as entering the pipeline. The one that you're probably most familiar with is Herceptin [trastuzumab], which is a monoclonal antibody to a gene called HER-2/neu. In patients who test positive for this gene, HER-2/neu, Herceptin has been a tremendous addition to breast cancer, both in the metastatic setting as well as in an adjuvant [post-surgical] setting with earlier stage breast cancer. There are many women who have been on Herceptin for years and are doing quite well. That's been a major breakthrough in the treatment of breast cancer. Sometimes we will combine Herceptin. In some cases, it is more efficacious if combined with hormone therapy in a woman who is hormone-positive, or with chemotherapy. It's got a synergistic effect [two or more drugs working together to get a better result].

Occasionally, we will use surgery or radiation therapy, even in patients who have far advanced disease. Generally, this is in palliation or to relieve a symptom. For example, surgery might be done for a woman with breast cancer that has a solitary brain metastasis, a brain lesion. Surgery is helpful sometimes for orthopedic issues. If there's a bone lesion [metastasis] and there's a risk of fracture, we may [surgically implant a] rod [in] a hip to prevent fractures. Sometimes surgery is necessary if there is spinal cord compression. We still do use surgery in some cases, even in far advanced disease.

Similarly, we use radiation therapy, generally in palliation or to relieve symptoms for a painful bone lesion or for brain involvement. We generally do not use radiation for organs such as lung or liver. There are many new techniques now in radiation therapy where one doesn't have to have a full course of therapy. For example, with the CyberKnife, sometimes radiation can be administered in one dose with the same effect in terms of pain relief.

Andrew:

Let's hear from Dr. Brufsky, who is co-director of the Comprehensive Breast Cancer Center and the medical director of the Women's Cancer Center at Magee Women's Hospital and the University of Pittsburgh Cancer Institute. He also serves as an associate division chief of the Division of Hematology/Oncology within the University of Pittsburgh School of Medicine's Department of Medicine. Dr. Brufsky will tell us about newer treatments for metastatic and advanced breast cancer, and also about ongoing clinical trials at centers around the country.

Dr. Adam Brufsky:

I take care of people with metastatic breast cancer for a living, and it's what I've done for the last 10 years. The strides we have made in 10 years really have been dramatic. Some things, such as Herceptin, have changed the way we treat women with breast cancer.

Everybody wants to either not get metastatic disease or, if they do, they want to live as long as possible with it or even one day be cured of it. Clearly, it's not something that happens overnight. Over the last five or 10 years, we look at each other and we go, 'Wow, we don't see as many women, say, with liver failure from metastatic breast cancer,' or 'Gosh, the women in our practice really are living longer.' It's not like with testicular cancer or childhood leukemia, where you just wake up one day and someone has a paper in one of our big journals that the cancer is cured. It's more that you take a bunch of incremental steps, and before you know it people suddenly are doing a lot better. That really is happening. It's hard for a lot of you to see that. But when you take a look at the global picture, it really is [happening].

What I'll do is I'll start with kind of the art of the possible, that is, what we're doing with current therapies to make them a little bit better for you. And then, I'll talk about some of the exciting new possibilities.

Probably one of the most important drugs that we have against breast cancer, if you're getting adjuvant chemotherapy or if you have metastatic disease, is the taxanes, and that's Taxol [paclitaxel] or Taxotere [docetaxel]. In 1963, 42 years ago, researchers at the National Cancer Institute found that the bark of a yew tree had anti-tumor activity, and to get Taxol approved took almost 30 years from discovering it as tree bark to getting it into people and getting it approved. That's how long sometimes it takes for drug development.

It was first approved for ovarian cancer. Breast cancer was almost an afterthought with Taxol, but in 1994 it was approved for the treatment of relapsed breast cancer. Docetaxel, which is from the European yew, was approved for metastatic breast cancer. About three years ago, a combination of Xeloda [capecitabine], which is an oral chemotherapy, with Taxotere, was approved. A year ago gemcitabine [Gemzar], another chemotherapy, [combined] with Taxol, was approved. And then finally, a novel formulation of Taxol known as Abraxane [nab paclitaxel], was approved also.

This is how development works. It takes a long time, but then we hopefully rapidly combine one chemotherapy with another to get more activity and less toxicity for people and more survival in metastatic breast cancer, or fewer women relapsing. We have pushed the taxanes almost as far as we can, and one of the newer things that we're doing is finding novel formulations that have less toxicity.

Taxanes in general are insoluble, so you need to dissolve them in something [in order] to inject [it] into you, so this [drug] would be soluble in your blood. Both with Taxol and Taxotere, the solvents have a lot of allergic reactions. Paclitaxel is dissolved in something called Cremaphor, and probably about 1 in 200 women will have a reaction to Cremaphor. It can be pretty severe, and in some women we can't give the drug to them anymore, even though it's very active. The same thing with Taxotere. It's dissolved in something called Tween 20 that people can get very bad allergic reactions to.

What Abraxis Oncology did is to solubilize the paclitaxel in this albuminized particle, so it's soluble [capable of being dissolved] in plasma. So there [are] no allergic reactions to it, and, most importantly, you don't need premedication.

A lot of women in my practice are on steroids, and that's worse for a lot of women than the chemo itself. 'God, Dr. Brufsky, why are you giving me steroids? I don't want them. They make me bloated. They make me wired. I go nuts. I don't want to take them.' Now, with some of these newer drugs, we can avoid that. This [Abraxane] is a new drug. Like anything, it takes a while to get into clinical practice, and a lot of us are starting to use it in our practices now. I think over the next couple of years, this will probably become more and more integrated into our practice.

Andrew:

What you're saying is you have powerful medicines like the taxane category. The refinement in this example is how it's delivered.

Dr. Brufsky:

Correct. It's delivered in the less toxic way, and that allows us to give more of it, so it, in some cases, can be more effective. What's limiting a lot of times with these drugs is we can only give a little bit, not as much as we'd like to because of limiting toxicities like allergic reactions. This allows us to give more.

Andrew:

Does it allow it to be a quicker infusion as well?

Dr. Brufsky:

It's about the same. It's about 30 minutes. In some cases for Taxol, it takes three hours. This can be 30 to 60 minutes, depending on the dose.

That's the art of the possible, what we're doing currently with chemotherapy. But the interesting thing about breast cancer, unlike other solid cancers like colon and prostate and lung cancer, is that just about any chemotherapy will have some sort of response. And the strange thing about breast cancer is that a woman can go through one, two, three or four chemotherapies, and on the fifth one she'll respond to it, oftentimes, for a long time.

As I tell women with metastatic breast cancer all the time, I may not be able to get rid of every single cell, but I can get rid of a lot of them, even sometimes in fourth- and fifth- line therapy. Never give up hope. There is always something you can do.

What causes women to become resistant eventually to the chemotherapy? If they respond to that fifth-line chemotherapy, why do they become resistant to it? It's one of the central questions right now in metastatic breast cancer. How do we find out what cells are resistant? How can we measure it, and what do we do once people become resistant? There's a variety of chemotherapies, drugs with novel mechanisms of action, like Herceptin [trastuzumab]. There's a new taxane [Abraxane] that works when you're resistant to Taxol or Taxotere. It also goes into your brain. That's a big problem with chemotherapies. They don't get into your brain, so a lot of women potentially can get disease in their brain even though the rest of the disease in their body is taken care of. There [are] drugs [in research] like epothilones. There's a drug called ixabepilone, which works very similarly to some of these novel taxanes if you're resistant to Taxol or Taxotere.

There are drugs called farnesyl transferase inhibitors, oral agents with very few side effects that may have some activity, drugs like Doxil [doxorubicin liposome], which is basically Adriamycin [doxorubicin] in a fatty container. It has less toxicity than the standard dose Adriamycin. Lapatinib is like an oral Herceptin. It inhibits the same protein that Herceptin binds to and may have activity in women who are on Herceptin. Various immunotherapies have been tried with mixed success, other than Herceptin. There are some interesting vaccines out there, but those are fairly far away. But there is a lot of excitement about things like Avastin [bevacizumab] and Herceptin and lapatinib.

Herceptin clearly has changed the way we treat metastatic breast cancer. The only issue that we're having is that we do such a good job with Herceptin and chemotherapy that women are now getting disease in their brain, and we're trying to figure out how to get Herceptin and Herceptin-like drugs into people's brains. That's probably the cutting edge of where we are in metastatic breast cancer right now. In fact, I petitioned the company and the FDA to try to give Herceptin directly into the spinal fluid, and they didn't like that idea. We're negotiating that right now.

Avastin is a class of drugs called angiogenesis inhibitors. It binds to a protein that's involved in the growth of new blood vessels, and it blocks new blood vessels from growing in cancer cells. If you don't get blood vessels and oxygen feeding the cancer, it dies. We were not very encouraged initially by Avastin. The initial experience with Avastin in clinical trials didn't work at all in breast cancer. It was a total bust. It took Kathy Miller, a medical oncologist at Indiana [University], to push the idea. We did a Phase III clinical trial in women who had already had a lot of chemo [treatments] before and gave them capecitabine, Xeloda, with or without Avastin. It didn't work that well, and we were ready to abandon it in breast.

But Miller pushed on, and we did a study of Avastin and Taxol in women with first-line chemotherapy who had never been treated before for their metastatic breast cancer, and it works. It almost doubles the time to progression [time before a tumor begins to grow again]. That was very exciting news, and it's likely to be approved [by the FDA] in the next six months for treatment of first-line metastatic breast cancer. It likely will have close to the impact that Herceptin did for HER-2/neu-positive breast cancer. We now have a drug for HER-2/neu negative breast cancer, and we're going to use Avastin since it works so well in metastatic breast cancer as adjuvant therapy, just like we're now doing with Herceptin. If you're a woman with HER-2/neu positive breast cancer, now we're giving you Herceptin to prevent recurrence. We're soon going to give you Avastin to prevent recurrence as well.

And two last things: The first one is circulating tumor cell measurements. There's something called cell search, and in Pittsburgh we're on the forefront of this technology. Instead of doing a CAT scan on you to see whether your cancer has grown or [shrunk], we can draw a tube of blood. And if you have more than five cancer cells circulating around in that tube of blood, your cancer is probably more active and potentially is progressing. If you have less than five cells, your cancer may not be progressing. [It's] a simple blood test, instead of doing a series of CT scans. This won't replace a CAT scan, but it'll be an adjunct. I'm sure some of you have the experience of going to your oncologist with metastatic breast cancer, and they're saying the scan kind of looks better, kind of looks worse, we're not really sure. This is a blood test that may confirm one way or the other whether your cancer is getting better or worse.

Oncotype DX is that last thing, gene profiling of tumor cells. A company in California came up with an assay where they take three small slices of your breast cancer. This is only for women who have lymph node-negative disease, who have breast cancer where the lymph nodes are not involved. They look at the expression of 16 genes, and they come up with a single number, a score. And if your score is 18 or less, you do not need chemotherapy. If it's 30 or more, chemo has a lot of benefit. If it's in between, we're not quite sure yet. But a simple test can tell you whether you need chemotherapy for your breast cancer or not. This is still in early development. If you have lymph node-positive breast cancer, receptor-negative breast cancer, we don't know what to do with that.

The bottom line is there [are] a lot of really neat new things in breast cancer, both in adjuvant therapy and metastatic disease.

Andrew:

[There are] just a couple of things I wanted to go over. One is, cancer is not an infection, it's like Dr. Susan Love says - your own cells gone haywire. And you're beginning to understand what's going haywire with those particular cells, which is what Dr. Brufsky was talking about - testing your own tumor cells and then having treatment that's right for you, as well as the benefit of preserving your quality of life even as you go through aggressive care.

Lauren Haag:

It was indeed.

Andrew:

So you had a lumpectomy, and you had how many lymph nodes removed?

Lauren:

Twenty-three. I had a positive node, so I was introduced to a clinical trial for early stage Herceptin, and I pursued that. We started with Adriamycin [doxorubicin] and Cytoxan [cyclophosphamide], and then with the Taxotere [docetaxel] I received Herceptin. For me, and everybody's different in their response, the Taxotere was more difficult than AC.

Andrew:

Related to Herceptin, the news from the ASCO [American Society of Clinical Oncology] medical conference was very positive. Dr. Marks, and by Lauren being in the clinical trial, she was part of that research very early on, as far as using it post-surgery, is that right?

Dr. Marks:

Yes, absolutely. And that's the way we make these discoveries is through clinical trials. The data is very encouraging in that Herceptin in an adjuvant setting actually improves survival by about 50 percent.

Andrew:

Wow, that was big news. I was in a clinical trial for my leukemia. And I would urge you if you have advanced disease, there's the leading edge of medicine moving forward. Not only can you help advance it, but hopefully it can give you great benefit too. Lauren was a pacesetter, as I was, in the trials that we were on.

Dr. Brufsky:

It's important to know, when you do a clinical trial, that at a minimum you're getting the best that we have. And at the maximum, you're getting something potentially better. So in the trial that Lauren was on, she got AC and Taxotere as a minimum. But she was able to get the Herceptin in addition, even though at the time we didn't know whether it worked or not. People don't understand that when we do trials. They think they're going to get something worse. It's never worse. It can't be worse. We have ethics boards and review boards that make sure that whatever trial we do is at least the standard of care, and it may be better.

Andrew:

You mentioned that you're combining drugs, and we mentioned this newer taxane, or Abraxane [paclitaxel]. That's in a trial that you're doing now, isn't it?

Dr. Brufsky:

We're about to start a trial of Abraxane for advanced breast cancer fairly soon.

Andrew:

So it's important to talk to your doctor to see if this trial might be helpful for you. Lauren, you work in the information technology field. Now, not everybody is an Internet whiz, but it sounds like you took a certain attitude about finding out what was right for you. And I know you participate in support groups online, and you've definitely found out you are not alone.

Lauren:

Absolutely, and I honestly don't know what it would be like to have this disease before the Internet because, for me, it would have been a completely different experience. I read a lot of books in the first few days after my diagnosis. My husband went to the bookstore and dutifully brought me home a big stack that I started to plow through. And then I found that the more current information was online. So I started to do a lot of research in my spare time and learned as much as I could possibly learn about the disease and about the treatment options. Like Dr. Brufsky said, I understood that clinical trials meant that next best thing, and so I wanted to be a part of as many of them as I could be.

Andrew:

I see Lauren as the picture of the proactive patient. If you could make some comments for women here, how would you coach if they're not the person who is accustomed to doing that? [Do you have] any tips for how they could gain support and have an active discussion with their doctors?

Lauren:

Just attending these sorts of events is taking a huge step in personal advocacy. But probably the most difficult part is talking to your doctor. I'm sharing the stage with two extremely bright people. And here I am, this nonmedical person. That just doesn't necessarily feel right. But that makes you feel like you have more control. For me, that was what I needed, a sense of control because I really couldn't control anything else about the disease. I felt that if I gained information and knowledge and helped participate in the process of administering my therapy, I could have some sense of ownership over the problem and hopefully help combat it.

Andrew:

Whether we have the Internet or you're in a support group and there's all this chatter going on, and your husband or a relative says, "We've got to ask the doctor this." Dr. Marks, you've been at this 25 years or more, and now we're all banding together as patients and trading information and wondering about this or that. There's a lot in the media. What's the right way, the respectful way, for a patient and a physician to have a dialogue?

Dr. Marks:

We're very open to frank discussions with patients. First, they have to listen to what we're recommending, whether it's a clinical trial or a standard form of therapy. But with so much information out there, it's quite easy for patients to get confused. Our patients come in with reams and reams off the Internet, trying to sift through and sort through what's valid and what isn't, and you've got to realize that there's a lot out there that isn't valid. There's a lot of voodoo medicine on the Internet, so you've got to be very careful sorting that out.

A lot of times that's my role, sifting through for the patient what's legitimate, what's a real trial, and what's worthless, and don't waste your time or money or energy. What I find now is women, in particular, are much more knowledgeable about their disease than they used to be. They do the research. They come in, and they ask the right questions. And, frankly, it takes more time. We definitely are spending more time with patients. But the result is positive, and I think the patients feel better when they leave, having a better understanding of their disease and their treatment, and also getting feedback from the physician about what they should avoid. That's been my experience.

Dr. Brufsky:

I would agree entirely. The Internet's been really active about 10 years, but the newest thing is that I have a BlackBerry. I have e-mail. If you're on the Internet and you're looking up something and it totally scares you or you're really interested in it, you e-mail me. And believe me, I don't mind it. It's a lot easier for me to handle an e-mail question from somebody. A lot of my patients e-mail me back and forth, and that directs what we do in the visit. It makes your visit with me a lot more efficient.

It's very easy to get overwhelmed with the amount of information. We always encourage people to get opinions, as many as you want. The problem is once you get two or three, it all becomes an information blur. It's the same thing with the Internet. You've got to be careful you don't get overwhelmed. Our role should be to help guide you through that morass.

Dr. Marks:

Those are two myths. Neither one is true. We have a nutritionist in the crowd who I may ask to comment when I'm done - Joyce, who is our nutritionist at the Hillman Cancer Center. But those are myths that have nothing to do with metastatic cancer. Sugar doesn't cause tumors to grow faster or to occur.

In terms of nutrition, we always emphasize to patients, you should have a well-balanced diet. You should take in plenty of protein and calories. When you have cancer, this idea of fruits and vegetables, forget about it. You know that just fills you up. There aren't any calories. There's no protein in it. Fruits and vegetables are great to prevent you from getting cancer 30 years later. But when you have cancer, and particularly when you're on active therapy, be it radiation therapy, chemotherapy, you need lots of protein, you need plenty of calories.

In terms of supplements, if you're on active therapy, particularly chemotherapy, you need to talk to your doctor about what you're taking because many of these vitamin supplements and "replacement therapies" can actually interfere with the chemotherapy and keep it from working. The problem is that many patients are embarrassed to tell their physicians that they're doing some alternative therapy, whether it's vitamins or what have you. You need to be frank with your physician and tell him what you're doing. If you're on chemotherapy, many of these things are dangerous. Even if you're not on chemotherapy, many of these supplements have their own inherent toxicities. Some of these agents can damage your liver, some are actually poisons. Talk to your doctor and consult with an expert, in these supplements.

Joyce:

My name is Joyce Diacopoulos. I'm a registered dietitian, and I work at the Hillman Cancer Center. I agree 100 percent with what he said. You all want to think that sugar in its purest form, glucose, is a form of energy. Everything we consume is going to break down to glucose. So it doesn't matter if you eat a slice of bread or a slice of cheese or nuts or yogurt, eventually the body's going to convert that to glucose. All our cells need glucose, not only cancer cells, but regular cells too. Glucose is a form of energy.

Now the acid-balance environment: I want to mention the kidneys are very wise organs that try to maintain a neutral environment. There are some nutrients that require an acidic environment for absorption, like iron, but, overall, an acid environment is probably not necessary for the majority of nutrients.

Andrew:

For a woman who's been diagnosed with breast cancer and has not had a recurrence, is there a diet you recommend to prevent that?

Joyce:

The American Cancer Society and the American Institute for Cancer Research promote what we call the plant-based diet, which doesn't necessarily only promote fruits and vegetables. It does promote lean cuts of meats and low-fat dairy products, along with whole grains. It also promotes a healthy lifestyle. If you're going to eat a healthy diet and smoke and not exercise, of course, that's not going be beneficial. Of course, alcohol consumption should be limited and try to reduce the stress in your life. Do some things that are very helpful and make you feel good.

Elaine from the North Hills of Pittsburgh:

I have had cancer for nine-and-a-half years, inflammatory breast cancer the last four-and-a-half years. And I had four recurrences the past four years. Right now, I'm on Abraxane [paclitaxel] and Gemzar [gemcitabine], which has been very successful, three weeks out of the month. Abraxane has been wonderful. You have some kind of normal life. I had 16 tumors in my liver, and now I'm down to six, and they are shrinking. And my bone cancer, thank God, has had very good progression.

Could you enlighten me about the other category of hormone therapy? Because, hopefully, when I get into remission I would like to know about that category.

Dr. Marks:

In the past, we used progesterone and androgen, male hormones, more frequently. But we still occasionally will use them, particularly in patients who don't have very extensive disease but have progressed on the series of hormones that we talked about. It's something else to try after you've been through multiple hormones. Androgens and progesterone, or Megace, do have some activity in breast cancer.

Darlene from the South Hills of Pittsburgh:

I am Dr. Brufsky's patient, and my concern tonight is my daughter. She is 24. I just saw my PCP (primary care physician) this week, and she said that my daughter should have that genetic testing. And if it's positive, she should have a double mastectomy. I would not even suggest this to her. She is just starting her life. I was horrified by that. My mother died of breast cancer after menopause. I am also postmenopausal. I have three sisters without breast cancer. I was so similar to Lauren - your beginning is exactly what happened to me. It's shocking. But I don't feel that my daughter, although she is an only child, is in any more danger than my three sisters, who also do not have breast cancer. I don't want to freak out my kid. She is just starting her career. She just graduated. She is in love. I would never, ever say that to her.

Andrew:

I want to put this in perspective. There's a test for BRCA-1 and 2, breast and ovarian cancer genes [that account for 10 percent or less of breast cancers]. There is a test for it. Genetic counselors or nurses or doctors will often work with you and plot out where the breast or ovarian [cancer] was in your family. How do you approach that in your practice?

Dr. Brufsky:

Did you take the genetic test?

Darlene:

No.

Dr. Brufsky:

The first question really is not testing your daughter, it's testing you. That's number one. The way we do this is we take women who have a strong family history, or maybe even who don't, who get breast cancer at a young age, and we have them meet with our genetic counselors. We have a genetic counseling service at Magee, as well as at Hillman Cancer Center. You meet with them, and they plug your family history in the computer, and they give you the odds that you have one of the genes for breast cancer, and then they'll offer you testing. The testing simply is a blood test that is sent off to a place called Myriad Genetics in Utah where they sequence the entire gene, looking for a single mutation. The gene is 100,000 base pairs long. One simple change can result in increased risk of breast cancer.

That takes about a month, and then they tell you whether you have the gene or not. If you were positive for BRCA-1 or 2, your daughter has a 50 percent chance of being positive. In your family, if your mother had been positive for BRCA-1 or 2, odds are that two of your sisters should have it, or you and one of your sisters, and two of them should not. Once know the mutation, then we send it off to other relatives if they want to be tested.

Now, 24 years old is pretty young. It may have come up in conversation with you and your daughter, and you have an idea of what she's thinking. But my general feeling, and unless someone strongly wants to do that at that age, I say live their life. The problems that you're going to get with breast cancer most likely are going to occur, if you're genetically susceptible, in your early to mid to late 30s - gives you time to have children, to, if you fall in love, get married hopefully.

Obviously, having the test would make this decision a lot easier because you'd have an idea. If she's negative, okay, you don't have to worry about it. She'll be like your sisters, that's even assuming you have the mutation. But if she's positive, they could increase surveillance. There are newer ways to detect breast cancer. You've probably heard that digital mammograms are better for young women. [There's] MRI testing for women at high risk - younger women with dense breasts. Those are the things I'd offer and have her live her life. I wouldn't immediately go to bilateral mastectomy unless she came and she said she wanted it.

Darlene:

Can I ask you a B part of that then? The "no mammogram until you're 40" routine, when I was doing my chemo, I met so many sweet, young women, and I hope some of them are still here today that had stage IV. And I said to them, "Why didn't you do your mammograms?" And it was because they weren't 40 years old. They were in their 20s and 30s. Do you personally want to change that?

Dr. Brufsky:

The reason they say that is that when you're young, you have a lot of estrogen. Your breasts are dense. It's very difficult with the older technology to detect lesions. With the newer technology, we may start to change that around. That's something that a lot of people are very interested in - MRI screening, digital mammography. I think people are rethinking those questions. If you have a family history of premenopausal breast cancer, clearly, I think you should be screened a lot earlier.

Darlene:

So you would say it's okay for her to wait?

Dr. Brufsky:

I think it's okay for her to wait, probably until at least 30. Even if she does a mammogram, her breasts are probably so dense that even if there was something small there, we may not find it. That's what the issue really is.

Andrew:

Lauren, you pushed to have the genetic test.

Lauren:

It wasn't something I pushed for, but it was something I did because I did have a family history on my father's side in my grandmother.

Andrew:

And you found out it was negative?

Lauren:

Yes, I did. One thing, Darlene, talking with the genetic counselor - if you wanted to learn more about how all that works, it's an educational process.

Andrew:

[There's] one other point I want you to observe here. We have some experts. We have an expert patient, who's been through a lot. But, certainly, two eminent hematologists/oncologists - no disrespect to the doctor - but go to experts. These are complicated issues. You're hearing about the leading edge of cancer therapy, and it's not something that every physician everywhere is going to know or understand. So when you have these big issues, go to real authorities. Make sure you feel comfortable that you have an understanding of these issues as you make decisions.

Camille from the North Hills of Pittsburgh:

I had surgery in 2003 - a lumpectomy. Stage I was my diagnosis. I had the positive receptor situation and the HER-2-negative. I'm on tamoxifen, and I'm premenopausal. I'm fascinated by Herceptin. Is that only for postmenopausal women, or would I be able to have that dialogue with my doctor?

Dr. Brufsky:

Herceptin [trastuzumab] is for when you're pre- or postmenopausal, but you have to be HER-2/neu-positive. If you're estrogen and progesterone receptor-positive and you're postmenopausal, we tend to use the other class of drugs called aromatase inhibitors – Femara [letrozole], Aromasin [exemestane], Arimidex [anastrozole]. If you're premenopausal, they don't work because they don't inhibit your ovaries from making estrogen. They inhibit the rest of your body from making estrogen. Really, we only have tamoxifen right now for women who are premenopausal.

Dr. Marks talked about Faslodex [fulvestrant]. We're thinking about using it in premenopausal women, but HER-2/neu is a totally separate issue. What we're trying to get a good feel for as medical oncologists is whether women with lymph node-positive breast cancer who are HER-2/neu positive should be Herceptin for at least a year. What we don't know is women who are lymph node negative - of those women, what should their risk be, should it be 1-cm tumor, 2, 3? We're trying to get a sense of who should get Herceptin and who shouldn't. But for your case, [the answer is] no.

Camille:

Because I am on tamoxifen and I have been for about a year-and-a-half now, I do take vitamin C 1,000 milligrams, and I take a prescription multivitamin. Am I okay to take that? I've been told by pharmacists that doesn't interfere with tamoxifen.

Dr. Brufsky:

You'll get a bunch of mixed opinions. A low dose of things like that is fine. But you've got to just show us. We want to see what you're taking. Just to talk to the dietary question, it's the commonsensical things that your mother told you [that are best] - a lot of protein while you're undergoing chemo, when you've finished your chemo, a balanced, but on the lower end of fat, diet.

There was a very large trial of 5,000 women just presented at our national meeting where half of them had a very low-fat diet. These were women who were diagnosed with breast cancer and had no evidence of recurrence. Half of them had a low-fat diet, half of them didn't. Women with the low-fat diet had fewer cancers. Now, clearly, the amount of fat that they cut these women to was very severe. It's very hard for people to do. But I think that any cutting of fat in the diet is probably a good idea. It's just when you get into megadose vitamin C, which is a lot of therapies out there as Dr. Marks and everybody knows. We want to see what you're taking.

Andrew:

In many of the major cancer centers, they have oncology pharmacists. They have dietitians who can help you. There's the oncologist you'll be seeing, but there's also the oncology nurse, the pharmacist, the dietitian.

Carol from Monroeville, Penn.:

In answer to Darlene's question about the genetic counseling, I went through that. My sister and my daughter and I were to go through that. And, unfortunately, the insurance would not pay for it. The doctor said, yes, you would be a good person to have in this study. But unless we can get your hospitalization to pay for it, he would suggest that we didn't do that. There was only like a 5 percent chance that mine would have been genetic because my mother had died of breast cancer. You don't want to put a monetary value to it, but you have to keep that in mind.

Andrew:

I have a question that relates to getting things paid for. With some of these newer therapies, are you having to battle the insurance companies, or are they understanding that for women with advanced breast cancer this is definitely something that should be supported?

Dr. Marks:

The insurance companies are obviously faced with the issue of the high cost of many of these new agents. Abraxane is a chemotherapy drug. We have not had any problems with reimbursement of that agent. But some of the targeted agents, like Avastin [bevacizumab] and Erbitux [cetuximab] and others, they do battle. These drugs sometimes are $8,000 or $10,000 a month, and they go by very strict criteria of what the drug has been approved for. For example, if we wanted to give Avastin in metastatic breast cancer, we'd have to battle with them.

Some insurance companies are more liberal than others. But because of the high costs of these new targeted agents, they are very cautious in terms of approving these. The other problem is that many of the newer agents are oral. They're pill form, like Gleevec [imatinib]. And many insurance companies, including Medicare, will not cover oral medications, so it's a real problem.

Carol:

Dr. Brufsky has me on Femara, and let me tell you I never had hot flashes until I took Femara - oh, my golly.

Andrew:

We've mentioned these three therapies - Arimidex, Aromasin and Femara. And for any of you who've been on tamoxifen have been told, you can only be on that five years. Where are we now as we have this new class of medicine as to how long somebody can take it?

Dr. Brufsky:

There was a trial a few years ago where women were on tamoxifen for five years, and we're trying to figure out what to give them after. Because it turns out that there are still a number of women who relapsed between five and 10 years after diagnosis. We can't really give tamoxifen for more than five years because there's an increased risk of uterine cancer, so we were in a bind. We decided to use the aromatase inhibitor, Femara. There was a large trial of about 5,000 women. Twenty-five hundred of them just had tamoxifen and stopped. The rest, the other 2,500, had five years of Femara. The trial was stopped after three years because the risk of breast cancer was cut in half by the Femara, and there were very few additional side effects. For that reason for most women who have had tamoxifen for five years, we usually recommend they go on Femara.

That's the first thing. There also was a very large trial of about 9,000 women who were postmenopausal who were initially diagnosed with breast cancer that was estrogen-receptor positive. Half got Arimidex, half got tamoxifen. After five years, the women on Arimidex had about 20 percent fewer recurrences than the ones on tamoxifen. So we've now changed that all women who start out will get Arimidex instead of tamoxifen. The final trials were trials of women who were on tamoxifen for two years and then were switched over - to Aromasin or to Femara or even Arimidex. There were three different trials like this, and in every one of those trials the women who were switched over to the aromatase inhibitors did better. So, clearly, aromatase inhibitors are now indicated for all postmenopausal women.

The three are interchangeable right now. We don't know which one is better. There's a clinical trial figuring out which of Arimidex or Aromasin is any better. And to Carol's question, what we sometimes do if people have really bad hot flashes with one drug is we switch them to another. Or we can control the hot flashes with some other medications.

The biggest issues really are two. One, they do cause osteoporosis. But our group just submitted to a major medical journal a very large clinical trial of drugs that can prevent osteoporosis from aromatase inhibitors. There's a drug Zometa [zoledronate], that's intravenous. You can take it once a year or twice a year. It's the equivalent of a year of oral Fosamax, and it will probably prevent osteoporosis. That's probably what's going to happen now - a lot of women are going to get that drug.

The [other] issue with them is their cost. The Medicare benefit, at least until 2006, doesn't pay for them. Arimidex is part of the Medicare Part II benefits, so it is on their formulary. But until then, it's tough. It's a couple of hundred dollars a month for it.

Andrew:

Related to advanced breast cancer, Dr. Marks, you showed those statistics, the five-year survival. With the kind of progress we're talking about, do you have a sense that we're rewriting history, if even incrementally, related to advanced cancer, that you can live with it and live better with it longer?

Dr. Marks:

Absolutely, those statistics were actually old statistics from the last decade. Probably the biggest change in metastatic disease has been Herceptin, which clearly is prolonging survival metastatic disease. And I think the next advance will probably be the addition of Avastin to early metastatic disease, as well as some of the other targeted agents. Erbitux is another agent out there that probably can prolong survival. There's no doubt in my mind that the five-year survival in stage IV disease is already better than what I showed you. We just need to demonstrate that. But with this pipeline of new targeted agents and new chemotherapy agents like Abraxane, those survival numbers will continue to improve.

Kathy from Murrysville, Penn.:

I am one of those people that are ER-negative. And you were talking about

Avastin. How do you determine who that is good for?

Dr. Brufsky:

We have no way of determining that. It's basically if you have metastatic disease, first-line therapy, you've had breast cancer before, it's now several years later, God forbid. You now present with disease in your lungs or liver or bone or lymph nodes - somewhere else. It'll be indicated for all women who are HER-2/neu negative in whom you'd think about using chemotherapy on. Right now, there's no test, like with Herceptin. We have the HER-2/neu test. We don't have a test for Avastin.

Lynn from Upper St. Clair:

I'm in my 12th year of treatment for breast cancer. I've been through a lot of the hormones that you listed, and I've been through a lot of the chemos that you listed. Do we have an understanding of why these different chemo drugs become ineffective after a period of time? And why do we never go back and try some of the ones that worked for us before? And since I had a treatment this morning, I have to sit down.

Dr. Brufsky:

That's the central question right now. Why you become resistant is number one. And number two is how to treat brain metastasis. Those are the two central questions in people who do clinical research in breast cancer right now. It's hard to know what that answer is going to be. You've got to do a hundred things, and maybe two or three of them will actually show promise.

A lot of us have started to think about cycling hormonal therapy, potentially going back, say, if you've had tamoxifen five years ago, have been through all the aromatase inhibitors, have been through various combinations, we've actually thought about going back to tamoxifen. Anecdotally, I've had responses in a few people. If you had Adriamycin five years ago and haven't had it for five or six years, maybe a drug like Doxil may be of benefit for you. There are people thinking, I've already had Taxol [paclitaxel] or Taxotere as adjuvant chemotherapy or chemotherapy for metastatic breast cancer five years ago. Maybe Abraxane is the right drug for you.

Is there any rationale to do it? No, there are no clinical trials to prove it one way or the other. But we owe it to you to at least give it our best shot.

Andrew:

Dr. Marks, isn't one of the areas that you're looking at chemosensitization, the idea that can you combine drugs to make the chemo more effective?

Dr. Marks:

There are assays or tests that are done that can determine chemo resistance, as well as chemo sensitivity. In terms of reliability, there's a lot of controversy. But there are a few companies out there that have the capability to test the tumor in a dish and see whether, in fact, the cancer cells are resistant or sensitive to a particular drug. We have a company locally in Pittsburgh called Precision Therapeutics, or PTI, that is developing technology to determine the sensitivity of cancer cells to one or a combination of chemotherapy agents. There are a few clinical trials that are underway using their technology. If we had an assay that could tell us ahead of time which drug was most likely to work, that would be very useful for patients.

Dr. Brufsky:

We're going to start probably within the next three or four months a small clinical trail in Pittsburgh with PTI with women with metastatic breast cancer. We will biopsy it and do the chemo sensitivity test and see how effective it is in that particular person.

Andrew:

Most adult American cancer patients are not in clinical trials, but there's a lot being investigated by these gentlemen and their colleagues. If you have advanced disease, that may help move the ball and also give you a shot at what could be tomorrow's medicine today. Could you, Dr. Brufsky, explain how can somebody enroll in a clinical trial? Let's say they're treated by a community physician. They don't want to give that up in a suburban community, but they'd like to participate in research, how do they do that?

Dr. Brufsky:

Pittsburgh actually is very unusual among communities in the United States in that we have a very close partnership with full-time academic oncologists, like myself, and the community oncologists, like Dr. Marks. And we've developed a very strong clinical trial system. The vast majority of our clinical trials for breast cancer, you can [participate] in the community. You don't have to come downtown. And that's unusual compared to some other cities around the country in that you usually may have to go downtown to the academic medical center to enroll in the clinical trial.

Usually, you've just been diagnosed, and you're interested in a clinical trial. You're about to get chemotherapy, and you're interested in a clinical trial, or you have had a relapse, and you're interested in a clinical trial. You bring it up to your oncologist. People just call me, and I will say, "Well, we have this clinical trial for this person."

Sometimes there are criteria that can be strict. We try to write clinical trials with very nonstrict criteria. But oftentimes there are very strict criteria, and there are trials that sometimes we can't get you on because you don't meet the exact specifications. It will hopefully be rare that we won't be able to fit you onto one of our trials.

Andrew:

I was in an Internet support group. And so as I was considering a trial, I actually got to correspond with people who were already in it. I'd call them up, and I said, "Give me the straight scoop." Lauren, what about you? Were you afraid of being in a trial? You've been in several, haven't you?

Lauren:

No, [it's] quite the opposite. I wanted to be in as many trials as possible because I truly felt it was the way to get the most advanced treatments. I certainly have spent a lot of time in online forums, meeting other people like myself. I learned about some trials through that process, and then you find your way to Web pages that have every trial everywhere, and you can research those.

I've used the Internet for two specific things. One is support, online support, and supporting others. That's been a huge part of my journey personally. The other side of that is collecting information. I spend a lot of time trying to read, but medical information as opposed to just doing a search and reading the first thing. If I find something that's of value to me or interesting to me, then I try to find that replicated somewhere. I look up more information around that. If I can find it five or six different places and they seem like reputable places, I'll look up the names of doctors and then I'll do a search of that doctor's name. I'll look up everything he's written. That's how I find out a lot of information that I'll then ask Dr. Marks about. So part of my research is really taking those paths.

Andrew:

Dr. Marks, just a word about clinical trials, this patient of yours, Lauren, has been in them. How do you feel about that, going down this road of investigation?

Dr. Marks:

I think it's great. We get answers to questions by clinical trials, and so we're always encouraging patients to participate when there's a trial available to them.

Andrew:

You should look into it, yes, ma'am. Let's take a couple of more questions as we wind down.

Sharon from Cranberry Township:

My mother was diagnosed with stage I triple negative cancer, ER-, PR- and HER-2-negative cancer. At the time of her surgery, we did submit a sample. It was to PTI here in Pittsburgh. And although it's rare, her sample had become contaminated, and we couldn't complete the actual chemo sensitivity test. Because she's ER-negative, she's also not able to do an Oncotype DX test. Is there any other testing that would available to her?

Dr. Brufsky:

No, how big was her cancer?

Sharon:

[It was] about 1.5 centimeters.

Dr. Brufsky:

And how old is she?

Sharon:

[She's] 63.

Dr. Brufsky:

Most of us, given that, would probably still give her chemo. Just because we have all these new tests doesn't supplant our clinical judgment or our experience with clinical trials.

Sharon:

We did do that. She's actually in treatment right now. We would just be interested to know whether or not it was the right one.

Dr. Brufsky:

I think that for a woman who has an estrogen and progesterone receptor-negative cancer at least 1 centimeter in diameter who can tolerate the chemotherapy, most of us in this town, and elsewhere, would probably agree to give her chemo. Most of us would probably recommend at least four to six doses of chemo with an Adriamycin-based therapy.

David from Upper St. Clair:

How useful is the CA 27-29 test in evaluating the effectiveness of chemotherapy drugs?

Dr. Brufsky:

We've gone back and forth with tumor markers. The CA 27-29 is a test that detects a circulating protein in your bloodstream that in a certain percentage of women, anywhere between 50 to 75 percent of women, is elevated when you have metastatic cancer. What a lot of us have done in the past is use that in conjunction with other tests. I usually use it in women where I don't have a good way of measuring whether the chemo is working or not. For example, in someone who has predominantly bone metastasis, it's very difficult to tell whether bone disease is getting better or worse on a CT or a bone scan. Because healing bone looks like bone that's being destroyed, so it's very difficult. Or in women with disease in their liver, but they have what we call fatty liver, so it's very difficult to tell whether the metastasis is getting bigger or smaller. I'll use a CA 27-29 with that as well.

However, this new cell search test is probably going to be better than that. That is what the cell search test is designed for, probably to replace the CA 27-29 in the evaluation of metastatic breast cancer. I don't use the CA 27-29 for routine screening of women who don't have any metastatic disease. Some oncologists use it and some don't. I use it to monitor the effectiveness of therapy, and I use it in conjunction with other tests.

Charlotte from North Hills of Pittsburgh:

We're honored to have with us Dr. Harold J. Burstein of the Dana-Farber Cancer Institute. And we're also very pleased [to have] Dr. Sheila Donnelly. Dr. Donnelly is a medical oncologist at Heywood Hospital in Gardner, Massachusetts. Our third panelist is someone who may be not so different from some of you. Denise St. Laurent is a retired financial advisor, also from Gardner, Massachusetts. She's been a breast cancer survivor since 1991. And as you'll hear, she's been in several clinical trials and has learned a lot about being a powerful patient.

Let's begin with Dr. Burstein, who will be giving us a brief overview of current treatments for advanced or metastatic breast cancer. Dr. Burstein is a clinician and a clinical investigator in the Breast Oncology Center at the Dana-Farber Cancer Institute here in Boston. He is also an assistant professor of medicine at Harvard Medical School, and he is involved in a number of major national breast cancer research efforts. He is on the editorial boards of several prestigious breast cancer journals, so he is very up-to-date on treatments and research.

Dr. Harold J. Burstein:

Many of us do a lot of speaking about breast cancer and breast cancer treatments. And we speak at medical conferences and things like that. But it's always a particular challenge to meet with families and breast cancer survivors and their friends, and to speak to the needs of patients who are living with advanced breast cancer because the issues that we talk about - how best to treat people, what progress is being made - are so acute for the needs of such people. One of the challenges is to bring what we hope is the right mix of enthusiasm and optimism and real excitement from the clinical world and the research world. We are going through an era when there are phenomenal numbers of new drugs and new techniques and approaches available. But, at the same time, we acknowledge with candor that these are treatments are imperfect and will not help many people, and that despite these treatments, many breast cancer patients will ultimately get sicker from their disease. I hope that we'll strike that balance for you and, at the same time, outline some of the broad themes that are going on in breast cancer medicine right now.

As many of you may know, mortality from breast cancer is declining, even though the number of cases of breast cancer continues to grow as we have better and more widespread screening programs and an aging population. There are more women affected by breast cancer, but the number of deaths in this country, and in most of Western Europe, have been declining for about the past decade. This is a remarkable testimony to tremendous public health efforts, principally in two major fronts: screening mammography, which has allowed for early detection of breast cancer in many women, and anti-estrogen therapies, particularly tamoxifen and drugs like it, which were introduced roughly 20 to 25 years [ago].

The other exciting thing is that we are in a golden age of clinical research. Many of you may read "The Wall Street Journal of Medicine," which is where most of the new information is released. Almost an avalanche of data from clinical trials and from the National Cancer Institute and the pharmaceutical industry tends to appear first in the major business journals because they often have such economic impact. But there really is a phenomenal explosion of approaches and new drugs in metastatic cancer and in metastatic breast cancer in particular.

The other thing that's happened as a sea change in approaching patients with advanced disease over the past decade has been a more profound appreciation for the supportive care needs of our patients. In many instances, we may be using drugs that are older drugs, but we are using them in dosing strategies that are better tolerated, that have fewer side effects, that are more convenient for the patient. And we've gotten better at taking care of the acute side effects of chemotherapy, things like nausea, vomiting, low blood counts, fatigue.

The earlier one detects breast cancer, the more likely one is to survive this disease. That's what contributes to the improvement in mortality - early detection through mammography and other strategies. Unfortunately, for stage IV breast cancer, the statistics are still quite sobering, with mortality on the order of 15 to 20 percent by five years after diagnosis.

For patients who have advanced breast cancer, the goals of therapy are to halt the progression of the disease, to bring it to its knees; to improve symptoms related to cancer burden, and those can be symptoms such as pain or cough or weight loss; to help people live longer and better.

We treat breast cancer based on the biology of the tumor. Breast cancer is the only solid tumor that we treat based on specific biological features of the cancer. In breast cancer medicine, one has to know the hormone-receptor status; that is to say, the estrogen-receptor status and progesterone-receptor status, and also the so-called HER-2 status of the tumor. There are probably four or five major kinds of breast cancer. We are increasingly recognizing that with some of the fancy new tools we have, and we can classify them based on their hormone receptor expression and on the expression of this protein called HER-2. In this regard, breast cancer is unique amongst all the solid tumors. For the most part, we treat all colorectal cancer the same way, we treat all lung cancer the same way, we treat all prostate cancer the same way. But [for] breast cancer, we tailor our treatments to the individual features of the tumor.

Roughly two-thirds to three-quarters of breast cancers are hormone receptor-positive. For those patients, we are often very successful using anti-estrogen or other hormone manipulations. About 15 or 20 percent of breast cancers are HER-2-positive, and for those patients we have a novel targeted drug called trastuzumab, or Herceptin, which is a monoclonal antibody that binds to the surface of the cancer cell and helps to control the cancer. We also have chemotherapy and some newer biological therapies, which we use for different kinds of breast cancer. But what distinguishes our success in breast cancer these days has been the ability to understand that there are different subtypes of tumor, that some will respond to hormone manipulations, others will respond to this new drug, Herceptin. Others, sadly, don't have targeted therapies yet, and that's what we're working on to try and do better.

Andrew:

Dr. Burstein, it used to be you'd say, "How big was the tumor?" And if you had surgery, "Did they get it all?" The way you're approaching it now, it's this biologic approach that is the way you view things.

Dr. Burstein:

It really is. Increasingly, we are talking about surgical or anatomic staging, which is to say, "How big was the tumor, how many lymph nodes were involved?" And then we're also thinking about biological staging - what are the biological features of this tumor that make it sensitive to chemotherapy or not, make it sensitive to hormone manipulations or not, and so forth. That really is a big shift in the way we've approached both early and late-stage breast cancer.

Andrew:

So if you can understand what characteristics there are, you can develop drugs for that. In the case of Herceptin, for that 15 or 20 percent of women who have that HER-2-positive status, that was a "designer drug" for that particular type of biology.

Dr. Burstein:

The other point about treating advanced breast cancer that differs from treating early stage breast cancer is that in advanced breast cancer we typically follow the patient's tumor burden. We follow their symptoms. We follow their X-rays. We follow their blood work to see if the treatments are working. And if the treatments are working, then we continue to use that treatment for as along as it's effective and the patient tolerates it reasonably well. If the treatment doesn't work for the patient, then we move on to something else.

In patients who have early stage breast cancer, they've usually had surgery, and we do not have any tumor to follow. We hope the patient's tumor is entirely gone and will never come back. We sometimes treat them with chemotherapy or hormone therapies to help make sure the cancer doesn't come back, but there's nothing that we follow. We typically say things like, "Well, you get four cycles of chemo, or you get eight cycles of chemo, or you get five years of hormone therapy." With advanced disease, we start out on this journey, and we see how things evolve.

Hormone therapy remains critical for women with advanced breast cancer. Hormone therapy was probably the first effective therapy ever used for any cancer. In the late 19th century, English surgeons began to take out the ovaries of women who had advanced breast cancer, and there were, in some cases, dramatic clinical responses. It was one of the first rationally used anti-cancer therapies, and now, 100 years later, we have a variety of hormone options available to us, though taking out a woman's ovaries, in younger women with advanced breast cancer, remains a critical piece of therapy in many instances.

We have a whole variety of anti-estrogen drugs. Tamoxifen [Nolvadex] has been the mainstay of therapy for many years. We now have a newer class of drugs called aromatase inhibitors that deplete the body of estrogen, but they only work in postmenopausal women. In premenopausal women, most of the estrogen comes from the ovary. In postmenopausal women, there is a lot less estrogen made, and it's made in tissues like the bone and the fat and the liver and the breast, by conversion of the male hormones like androgen into female hormones like estrogen. The enzyme that does this is called the aromatase enzyme. You can poison that enzyme with these drugs, and the wonderful thing about these aromatase inhibitors is they are very selective. They have hardly any side effects except for those related to the depletion of estrogen, like hot flashes and night sweats and vaginal dryness, and even osteoporosis.

We have some newer drugs coming along, injectable drugs like fulvestrant, or Faslodex, which is another pure anti-estrogen. It binds to the estrogen receptor in the cancer cells and causes the receptor to be degraded by the machinery within the cell. Some older drugs, like Megace [megastrol], or even androgens, male steroid hormones, can help control tumors. It is typical for a woman with an estrogen receptor-positive breast cancer to be treated with three or four different kinds of anti-estrogen therapy in succession, one for a long time. Then perhaps things go forward, you switch to another, and you go back and forth to try and control the tumor for as long as possible.

For these estrogen receptor-positive tumors, we think of estrogen as a fuel or a stimulant to the growth of these cancers. Depriving the tumor of estrogen, depleting the body of estrogen, is a very successful strategy.

The other big tool that we have is chemotherapy, and there is a list of about 15 or 20 chemotherapy drugs, which are effective in advanced breast cancer. And, additionally, about a half dozen chemotherapy cocktails or combination chemotherapy regimens are also very effective. Many of these drugs are actually quite new. Some of the drugs, like the taxanes, were developed in the 1990s. Drugs like Xeloda [capecitabine] were developed in the late 1990s. So there are constantly new chemotherapy drugs coming along with activity in advanced breast cancer.

For old drugs, we are getting smarter about how to give them. For instance, Xeloda, which is an oral form of a drug called 5-FU, was a real advance for two reasons. One, is it's a convenient way of getting chemotherapy. It's given by pill, so you're not tied down to the doctor's office every week or two for chemotherapy. It's the same drug as 5-FU, 5-fluorouracil. But because it's orally available, patients can take it at home, and it probably works a little better. In the old way, we gave patients a squirt of the 5-FU in the clinic, and it lasts about 30 minutes before it's all destroyed in the bloodstream. Whereas, with the oral Xeloda, it's a chronic, repetitive, daily exposure, and that probably actually makes the chemotherapy work better.

Another example of this would be some of the derivatives of some older drugs. There's a drug called liposomal doxorubicin [Doxil] or another drug called nab paclitaxel [Abraxane]. These are second-generation chemotherapy drugs that have safer side-effect profiles for patients. The third example I would draw your attention to is a drug called paclitaxel, or Taxol. Taxol is a widely used chemotherapy drug for lung and ovarian and breast cancers. But what we've learned in the past couple of years is that by giving lower doses of Taxol on a more frequent schedule - weekly Taxol compared to a large dose once every three weeks - we take the exact same drug and make it more effective. We make it better tolerated because the patients get less of a big slug, but they get a more bearable treatment every week or so. So we have new products that are coming along, which is exciting, but we're also learning how to use some of these older products to maximize the efficacy and the tolerability.

In terms of what's sexy out there in breast cancer medicine, the biologic therapies remain the hottest new items on the market. What we usually mean by biologic therapies are some of the newer drugs that target some of the intrinsic growth properties of the cancer cell but which lack the side effects of chemotherapy - that is to say, they don't make people so sick to their stomach, they don't make people's hair fall out, they don't make the blood counts get so low. The hope is that building on the revolution in biological science over the past many years we can be smarter about targeting specific steps in the cancer process.

We've been quite successful with that in a couple of examples in breast cancer. The exemplar for this has been Herceptin, a monoclonal antibody. We all have billions of antibodies in our bodies. They're designed to help the immune system work better. They are proteins, and this is a humanized monoclonal antibody. They purify the stuff and clean it all up, so it's pure protein, and they inject it into patients. When you give Herceptin to patients with HER-2-positive disease, it has a dramatic impact on survival. It really seems to be able to cause the cancer cell to undergo apoptosis, a fancy biological word for programmed cell death. It also seems to make chemotherapy [work] better. When this drug first came out, everybody wanted Herceptin, of course, because it doesn't make you sick, it doesn't affect your blood counts, it's not chemo. It's really quite astonishing. But the wrinkle is that it only works if the tumor is HER-2-positive.

What you see with these biological therapies is we are fragmenting breast cancer into different diseases. There's HER-2-driven disease, there's estrogen-driven disease, and we're trying to go after these. There are other biologic therapies coming out. And inspired by Dr. Judah Folkman, who is one of the investigators in our medical center [Dana Farber] there's been a lot of work in angiogenesis inhibitor therapy. This was on the cover of Time magazine about a year ago. The argument here is a very simple one, and that is that tumor cells, like all normal cells in the body, require a blood supply because they have to get oxygen and nutrients just to stay alive. Just as an army can't live without a supply chain or a plant can't live without roots to bring it nutrients, a tumor cell needs a blood supply. And one of the clever things tumors do is induce blood vessels to grow towards them through the release of angiogenic factors - new blood vessel formation factors.

We are now testing a large number of anti-angiogenesis drugs in breast cancer, and one of the first to be well-characterized was a drug called bevacizumab, or Avastin, which you may have heard about as treatment for lung or colorectal cancer. At the ASCO (American Society of Clinical Oncology) meeting in May of this year (2005), there were dramatic data that by adding Avastin to chemotherapy you make the chemotherapy work better, and you can prolong survival for patients with advanced breast cancer. So this is another whole field of targeted research, trying to choke off the blood vessels that may be growing to feed these cancer cells. [Medical editor's note: Avastin is currently only approved by the FDA for the treatment of colorectal cancer.]

Andrew:

Is that true with cancer cells that they have their own network of blood supply different from the healthy cells, so if you have a biologic agent that can inhibit that blood supply to the cancer cells, you're not hurting the healthy cells?

Dr. Burstein:

That is about two-thirds true. On the one hand, cancer cells can travel through the normal blood supply of the body, and, sadly, that's how they can move around and lodge in different parts of the body. If that was all that happened, you would never be aware of the cancer problem because we're talking about microscopic burdens of cancer. Anytime a cancer cell grows to beyond microscopic size, really the size of a grain of salt, you have to get a blood supply to it. And it is exactly right then that the cancer cells seem to drag this inappropriate growth of blood vessels toward them, which allows them to be nourished and grow, and that is what we're targeting. It's the same. The challenge is to poison the bad blood vessels without killing off all the essential blood vessels. It seems that we can make some headway with these newer anti-angiogenesis drugs.

A couple of other areas where we're helping patients do well with advanced cancer: Sometimes the cancer goes to parts of the body where either chemotherapy doesn't penetrate well or other treatments can be helpful. A classic example of that in breast cancer would be bone metastases. Bone metastases can be quite painful, and judicious use of radiation therapy can be very helpful for alleviating the pain that people have in their joints or in their bones from advanced breast cancer.

The other thing we're doing for patients who have bone metastases with advanced breast cancer is using bisphosphonates. These are medicines that you may know very commonly as treatments for osteoporosis. Fosamax [alendronate] is a very commonly used drug in postmenopausal women for osteoporosis. What we found in cancer medicine is that using "high octane" versions of Fosamax allows a mesh to be formed in the bone, which stabilizes the cancer lesion in the bone and can alleviate pain and prevent spread of the cancer within the bone. This is not chemotherapy. It's not directly targeting the cancer, but it's an example of a supportive measure where we can help patients have less pain and do better by treating their bone metastases.

We are doing better against advanced breast cancer. We all wish it was a Barry Bonds moment, that it was a home run, that you just knock one out of the park and walk off the field and go home. That really isn't how we've made progress though. What's made progress has been chipping away at the problem, going at it from different angles and strategies, and putting these together. At the same time, we have a lot of new drugs available to us, we are also using older drugs more wisely. And that has meant that the experience of getting treated for advanced breast cancer continues to be far more bearable than it was in years past.

Andrew:

You mentioned bisphosphonates. Are you finding any anti-cancer properties of those?

Dr. Burstein:

It has been argued that these medicines, bisphosphonates, not just make people have less pain, but actually could have direct anti-tumor effect. That's being studied in some very large trials that are ongoing right now. There's been some preliminary suggestion from European and German studies that there may be this anti-cancer effect. We've not quite been convinced about yet, so it's an area for active investigation.

We wish you all the best, Denise, and we want to check back with you as you continue a journey with advanced cancer that is inspiring to many other women. You're a great example. Thanks for being with us today on the Breast Cancer Education Network. We wish you well.

What are the options once resistance develops? There are many new compounds being investigated. I mentioned Abraxane, but there are new drugs called epothilones [ixabepilone is one in clinical trials], which are similar that may have slightly different mechanisms of action and may work in patients who have progressed on taxanes. We're looking at various combinations of Avastin [bevacizumab] with some old drugs. Oral Cytoxan [cyclophosphamide] and oral methotrexate, which have been around for 35 or 40 years, are being used and studied in conjunction with Avastin as a way of trying to combine chemotherapy with an antibody so that you're trying to attack the tumor on more than one front.

There are liposomal agents. Again, this is a packaging device. This is a way of putting a drug like Adriamycin [doxorubicin] into a form which allows a slow release, which makes the toxicity different but usually much less and may allow a constant exposure to a drug, which might produce a response [Doxil is liposomal Adriamycin].

One of the caveats that I would throw out is that sometimes when some new treatment hits the press, it's good news, but it can be a disappointment to you as an individual because it may not apply to your particular cancer. For clinical protocols, there are inclusion and exclusion criteria. Patients might hear about some new drug, and they're very enthused about it. But it turns out that because they have been pretreated with so many drugs, or because their kidney function is impaired, or because they have underlying heart disease, or neuropathy, they won't be eligible. The last thing you want to do is be let down tremendously because it may not apply.

Where are we going? Certainly, there is great enthusiasm about doing gene profiling of tumor cells to be able to tailor therapy a bit better to the individual. We know, for example, that we've got these targets like estrogen receptors and HER-2. There must be many other targets that could predict whether your tumor would respond to a certain chemotherapy agent or not, rather than testing it in you by trial and error to see whether or not you're the one in four who's going to benefit from that particular treatment. This is even now being applied in the early stages of breast cancer to try to predict whether hormone therapy is sufficient to treat certain women, or whether additional treatment might be beneficial.

Right now when you embark on a chemotherapy regimen, you need to be able to sit tight for a couple of months and have repeat clinical staging. If a tumor is visible or measurable on a physical exam, you're sometimes going to know in six to eight weeks is it shrinking or not? If you don't have something on the outside, you depend on CAT scans or perhaps a chest X-ray, and you really need time to evaluate whether that drug is doing any good. If you could say to the patient 10 days or two weeks after the first cycle that, "I have measured tumor cells before we started and I've measured them today and now you have less than a certain number, therefore we know this drug is going to work," you wouldn't have to go through the side effects for a couple of months if you knew it was not going to help you. There's great interest in developing measurements such as that. People's tumors are different. You can't predict from person to person at this point ahead of time whether a particular agent will be useful. This is where more targets will be very helpful.

Andrew:

Denise, you've been on your own journey, trying to learn about a disease that you didn't know much about since 1991, when you found a lump. You had surgery, and then lymph nodes were taken. You had a modified mastectomy?

Denise St. Laurent:

Partial mastectomy with a lumpectomy, and then taking out some of the nodes. And, at the time, they were doing studies on whether they would take out a lot of nodes or just do a few. They took out six, and there were three positive and three negative, so they stopped.

Andrew:

This was 14 years ago. So you had chemotherapy and radiation after that, and then did you get a break for a while?

Denise:

Yes.

Andrew:

How long was it before you found it the second time?

Denise:

Just about when I came off of tamoxifen, at that five-year point, I already was starting with symptoms. The only symptom that I had was my eye - there is a little droop in it. They called it Horner's syndrome, and it's still with me. I've had it for a long, long time. [Medical editor's note: Horner's syndrome is seen in a variety of conditions, one of which is cancer that has spread to the brain. Sometimes brain metastases can be treated with localized radiation.]

The only other symptom I had I didn't really know was a symptom. But if you have a charley horse in your leg and it tightens up, I would have that in my shoulder [and] wake up in the middle of the night with that excruciating pain.

Andrew:

Denise, you had a third recurrence in your chest, and you had radiation and treatment for the metastases in your chest.

Denise:

I had a lot of the things that they just talked about - probably the whole laundry list, actually.

Andrew:

Are you on treatment now?

Denise:

Yes, I have had the Abraxane, Xeloda, Faslodex, Arimidex.

Dr. Sheila M. Donnelly:

And [you had] high-dose therapy in 1997.

Andrew:

Denise, you definitely have investigated these therapies. It seems like you play a very active role in your care.

Denise:

I did [take an active role] from the very beginning. I got involved with calling that 1-800-4cancer, which brings you to the National Institutes of Health. I found out that there's the patient's side, and they also had something called PDQ, which was it physician's data query. I found out that if I fooled with my computer, I could get both the doctor's side and my side. What I really wanted to know is, was I getting the standard therapy here that I could get across the country? And I found that I was.

Andrew:

What advice would you give people? You got very involved, studied up on things. Do you think that's helped you now over so many years fighting breast cancer in trying to put yourself back in control?

Denise:

Taking control was probably the first and the best thing I did. First of all, you're getting all these treatments. I got CMF, which is Cytoxan, methotrexate, 5-FU. I got the Adriamycin and Taxol over the years, and high dose of some of the taxanes. It's just like putting poison in your system, and you're having to deal with all the side effects. You have to be alert because you may get too many of those.

Andrew:

Denise, you've had wide experience with all this. The journey of our listeners may be different. What's the common thread for the role of the patient in helping them get the best and most modern care?

Denise:

It's taking control.

[Learn more about Denise's breast cancer journey in this extended interview.]

Andrew:

Denise and I would both say to you that you need to get smart and ask questions. Dr. Burstein, you'll agree that people with advanced breast cancer and you as a researcher are on a journey together.

Dr. Burstein:

That's one of the remarkable things about your [Denise's] story and so many other women is that it is a journey. Some paths you are able to go on for a long time very successfully. Others become dead ends rather abruptly, and you have to move on. One of the great uncertainties that women with advanced breast cancer face is you don't know when you start out what it's going to be, and that is emotionally very challenging for our patients.

The other thing that your experience exemplifies is the opportunity to participate in clinical research, and sometimes those are wonderful opportunities, and sometimes they are opportunities that are perhaps toxic or ineffective. But for most women, there will be, at some point in their treatment, the opportunity to think about a clinical trial, and certainly I hope many of you consider that.

When I listen to your story it is very familiar. You have Dr. Donnelly. You have a good doctor, but there are the small pieces and the big pieces. There [are] the symptoms and figuring out what's going on. And then [there is] treating something with radiation and something else with hormone therapy and then trying some chemotherapy and then back to radiation and then maybe a clinical trial and then maybe more hormone therapies. That's the art of being a medical oncologist, and the challenge for the patient is to sift through the reams and reams and reams of information that are available to you and try and work with the doctor on that path.

I would echo what was said earlier about the Internet. It is astonishing how much information you can get on the Internet about breast cancer and clinical trials. One of the things the government does very well is make information available through the National Institutes of Health, and the Web site www.cancer.gov is the public's portal to tremendous amounts of information on cancer. Your experience is very familiar - which is after you've been through it a couple of times, you're ready for the professional's piece.

It's like the way I feel about home renovations. I cannot screw in a light bulb. I love watching those shows - Bob Vila and all those guys. They're always pouring concrete and putting in these fabulous shelving units and redoing their furnace. And my wife laughs because I can't do any of it. But I like to know what they're doing. You need to know enough, and then you also need to trust who you are working with. You will feel more trusting if you know something, and work with the doctor to know what's really right for you.

Dr. Donnelly:

I wanted to comment on clinical trials. When patients sign up for a Phase III randomized trial where you're getting either the standard treatment, which was chemo, or the standard plus Herceptin, you don't get to choose which group you're in. You are selected by a computer number. If you enter a clinical trial like that, you have to be willing to go with whatever you're assigned. Nor can I, as your physician, say, I think you should be in the Herceptin arm. That would obviously make the clinical trial biased. So you have to be a little bit of a gambler, and when they turn out positive, and you happen to be in the experimental group, you're a winner. If all you got was extra toxicity and bad side effects and then it turns out at the end of the trial that there was no difference, then you're disappointed.

This is the hard thing with breast cancer because we have so many good treatments that for people in the community who live great distances from centers, it's very easy for them to choose an agent that's right there that can be given in their community hospital. It's different if you're at the stage of the disease where these conventional agents have only limited expectations. Then, it's much more attractive, and patients become risk-takers and are willing to go onto new treatments. Breast cancer patients have many, many choices. I think that makes it even more confusing. It's not just what to try, but at what stage you're going to do it. Are you at a point in your life where you want to be doing something besides spending a lot of time at the hospital? Would you rather go on a conventional oral agent and have rather predictable toxicity, even though you know that's not going to cure you, or are you willing to take a risk and be in something that holds that promise, the carrot, of maybe you could win big? All of these things have to be very carefully thought out.

Dr. Burstein:

As soon as a doctor is asking you to consider deviating from the straight and narrow, you really need to understand why there are limitations to the options in front of you and why the doctor is interested in thinking about a nonstandard treatment.

There is a temptation for patients to get much of their care and then think about clinical trials as a last-ditch effort. But sometimes it doesn't work that way, and the development of this drug Avastin [bevacizumab] in breast cancer that we've been alluding to this evening is an interesting study in that. The study that was first done with Avastin was for women who had had a lot of chemotherapy, and their tumors were very advanced and refractory [not responsive to treatment]. They did a trial of Avastin in that setting, and the drug didn't work. There was a lot of discouragement about Avastin in the breast cancer community at that point. The National Cancer Institute funded another study to use Avastin in women with metastatic breast cancer, but who'd had less chemotherapy to date - earlier in the course of their journey. That's where Avastin emerged as a valuable intervention, so it is not always the case that it is best to wait till the end to try newer ideas. [Medical editor's note: Avastin is approved by the FDA for the treatment of colorectal cancer, but is not yet approved for use in breast cancer].

Augusta from North Andover, Mass.:

I'm a 17-year breast cancer survivor and a 21-year bone cancer survivor. It was not a metastasis from breast to bone. [It was] two separate cancers - a chondrosarcoma of my right tibia. I just want to piggyback on what Denise said. I admire her, take my hat off to her. She's absolutely 100 percent correct. Take charge of your health. You take charge of it. Become a partner with your doctor. Like Denise, she's done all of her research, got all of her facts and came to the table with some information, which was excellent because if you're not a partner with your doctor, it's the same as playing football. I don't know that much about football, but I know when the players get together in a huddle, they don't talk about what they did last week or last night. They talk about the next play so that every member of the team knows exactly what's going to go on.

Take a friend with you to the doctor because sometimes you're so set on one thing - do I have cancer, do I not have cancer? And that's all you hear. Everything else goes above you, under you and around you. Take someone who's not so emotionally involved in it so that they can be an extra set of ears for you.

Dr. Burstein:

The goal, especially for advanced cancer patients, is to preserve life as normally as possible. There's not tremendous value in helping people live longer if that time is all spent in bed, in a hospital, feeling crummy. All of us take pride in helping our patients get through these experiences. Nothing makes us happier than when they come in with pictures from family events and the Red Sox game because we want things to be as normal as possible for as long as possible.

Augusta:

There's one other thing I'd like to share with the group. Don't develop that shake-head syndrome. When you're in with a doctor and you don't know what he or she is talking about, ask questions. And go to the top when the bottom doesn't work. If you advocate, fight for yourself. You will survive.

Andrew:

If you're talking about the insurance issues, you may be told no along the way and there's an appeals process, there are state insurance boards. Probably each of you have had an experience [of], "We're not paying for that." You have a lot fire power being an advanced cancer patient.

Dr. Burstein:

Just to elaborate on that as it relates to clinical trials, most all clinical trials are set up so they will not cause patients more money out-of-pocket. The sponsor of the trial swallows the cost if there are extra tests, and most insurance plans fully support participation in clinical trials. Provided that you have access to some insurance or state welfare, you wouldn't forfeit any opportunities to participate in studies.

John from Plymouth, Mass.:

I have a question about hormonal therapy. It's a twofold question. Regarding aromatase inhibitors, you mentioned three different types, and I'm wondering what the differences are and whether or not one may be more effective given a particular set of circumstances than another. And once a drug such as that stops being effective, does that mean its use in your therapy is done forever, or could you circle back to that same drug and find it becomes effective again?

Dr. Donnelly:

There are three aromatase inhibitors that have been approved since 1995 for the treatment of metastatic, and in many cases, adjuvant breast cancer treatment. The brand names are Arimidex [anastrozole], Femara [letrozole] and Aromasin [exemestane], and although Aromasin is in a different class from Arimidex and Femara they basically have the same track record, the same toxicity profile, and it's very hard to choose one over the other.

In general, you don't go from one to the other as the disease progresses, with the exception of some patients who started out on either Arimidex or Femara, which are in the same class. If they have very slow progression of disease and the patient isn't in real trouble, but you need to make a switch, you might switch them to Aromasin because there have been some trials that have looked at that sequence and show that maybe 20 to 25 percent of people will benefit. By that, we mean they either have their tumor shrink, or it stabilizes for a period of six months. In metastatic breast cancer when you look at clinical benefit from chemotherapy or hormone therapy if you have stable disease for six months, you're as apt to have improved survival as the person who has an objective response.

In terms of their usefulness, the only time I'll switch around is if a patient's having a side effect, and I'm wondering if they might try one of the other ones and tolerate it a bit better.

Dr. Burstein:

Would you use the same drug again?

Dr. Donnelly:

In general, you don't because you usually don't have the opportunity. But we all have patients in our practices who have had metastatic breast cancer for several decades. How it is, I don't understand. I can think of an individual woman I've presented at case conferences as a way of teaching fellows. This woman has cycled through all known hormonal therapies and is revisiting them. Those are unusual patients.

Something that's rather commonly done would be a woman who had received tamoxifen for five years as adjuvant therapy in her early treatment and then stopped it, and let's say five years later had developed a recurrence. She's hormone receptor-positive. She could still respond to tamoxifen. Now, we might choose to use the aromatase inhibitor, but before we had them we would have gone back to the tamoxifen. So there [are] all different circumstances where you might recycle them if you have the right kind of disease.

Andrew:

While you've had various bumps along the way, Denise, you're here today and living pretty well. There's a lot of art in oncology. We have these studies. You have an active dialogue with your doctor. There's a lot of opinion. You have physicians who have been practicing quite a while, and they have their own experience, and they draw on that in consulting with you, but some things are not at all clear-cut. Wouldn't you agree, Dr. Burstein, that's where the art comes in - the active dialogue between the patient and the consulting physician?

Dr. Burstein:

Absolutely, even with standard therapies, you have be a little willing to try things and go back and forth. There's an old joke in medicine that if you see one case it's an anecdote, two cases is a case report, and three cases you're the world's expert. It helps to have a little bit of experience in these things because it gives people ideas to try.

Mary Lou from Syracuse, NY:

I'm wondering whether anybody could give me some additional information about genetic research above and beyond the BRCA-1 and 2. Where are we, and what is it looking like?

Dr. Burstein:

Many women when they're diagnosed have a family history of breast cancer, and they may have had cousins or aunts who had breast cancer. But for these families where there are many first-degree relatives - that's mothers and sisters - going back over generations who had breast or ovarian cancer, there is sometimes a hereditary predisposition, a gene defect that one is born with that predisposes to getting a breast and/or ovarian cancer. That is about 5 or 10 percent of all cases of breast cancer, and for about half of those cases we think we know the genes that are at fault, and these are the so-called BRCA-1 and BRCA-2 genes. One can get tested to see if you have a gene mutation. Women who have bilateral breast cancers, women with strong family histories of breast and ovarian cancer, young women diagnosed with breast cancer, are all far more likely to have these inherited gene syndromes.

The question relates to our gap in information for the other half of these very clear hereditary cases. Sometimes we will see women where their grandmother had breast cancer and their sister has breast cancer and they have breast cancer, and we do the genetic testing [for BRCA 1 and 2], and it's normal. The presumption in these cases is that there are other genes that contribute to this familial risk, but we don't have the tools to characterize them. So at Dana-Farber and at major cancer centers like it, we have a high-risk and genetic cancer program. Ours is headed by a lovely woman named Judy Garber, who many of you may have met or know. One of the goals of our program there is to help women understand the genetics of their disease, to do genetic testing, and understand for the future what are the other genetic contributors? The research to date suggests that there probably are other genes, but it's going to be much more complicated than the BRCA-1 and 2 story, and that's already a pretty complicated story.

When you start to get to multigene interactions, you probably have several genes that are trafficking in a family line. There is some interaction at some point, and this does increase your risk compared to the average person, but it's been very tricky to sort out, so it's still very much a work in progress.

Andrew:

Dr. Donnelly, you mentioned that there are new tests, particularly in early breast cancer, genetic tests looking at the genetic injury that's in that cancer cell. This is different, right? In one case, we're testing for hereditary connection. In the other case, we're trying to understand the genetic type of cancer that you have, whether or not there was a hereditary connection. Is that right?

Dr. Donnelly:

Right.

Andrew:

Are you encouraged? Some years ago, maybe you didn't have this vast [treatment] armamentarium. How are you feeling about things?

Dr. Donnelly:

I don't think you should be in this business if you're not an optimist, and I am an optimist. I've been in it long enough to see real progress. Survival is better, the cure rate is higher, people are living with this disease longer. And I would love it if the breakthrough came tomorrow. But none of our breakthroughs have been in giant quantum leaps. You're chipping away at this disease, and one trial builds on the next. One trial will show a 3 percent advantage. That doesn't sound like much. But if you compile that over the years, you're curing more women of the disease. The clinical research, the basic research, that has been going on for the last 10 years is starting to pay off at a clinical level, and I would certainly predict that that would be ongoing.

Denise:

I'm very hopeful. We talked at length about quality of life. And right now, I'm golfing and I'm swimming and I'm enjoying my family more and taking more time with them. That's a good thing. We talked about, well, if that's not the case, then we'll discuss not taking any treatment. But as long as you can manage, if you have minimal side effects, some nausea now and then, and fatigue, or no hair, oh, well, [that's] the story of my life. I've been with no hair for a long time. But, hey, my nails are nice.

Andrew:

Dr. Burstein, when you look back on all these things, do you think we really are making progress?

Dr. Burstein:

There's no question, and I hope we've given you a sense of that this evening. I have a bit of scholarly interest in the history of medicine. And you look back, and you scratch your head, and you say, "Can you believe they used to do that?" I think that we are right at a moment of tremendous explosion in how we treat advanced cancers of all kinds, and the tremendous gains in basic biological understanding over the past 15 or 20 years are finally reaching the point where we can translate that into clinical experience. We have better molecular tests for diagnosis. We have new molecular tests for how the patient's responding. We have new drugs that are built around a better understanding of the cancer cell. And the expectation is that that progress is going to continue very fast. It's never as fast as we would like. It's never as fast as you would like, but it really is happening. As a testament to that, the treatments we've been talking about here that are all standard treatments for advanced breast cancer are more or less things that have been developed since 1995, which is only 10 years ago. I echo what Sheila [Donnelly] said, that you have to be an optimist in this business.

Andrew:

I really want to thank all of you for joining us tonight, and we want to thank the organizations that have helped us raise awareness for this: the Dana-Farber Women's Center, the American Cancer Society, the Susan G. Komen Breast Cancer Foundation, and the Oncology Nursing Society. From all of us at HealthTalk, we wish you and your family the best of health. I'm Andrew Schorr.]]>

Andrew:

Now, you were participating in various research, clinical trials. Was that difficult for you, or was that something you really wanted to try because you were frustrated with the recurrence of the cancer?

Denise:

Well, there was no study that could prove one way or the other what was the best. At the time, I had a friend who had had a stem cell transplant, and she was on my case, "You better do this, you should try it." At that point, she was five years out, cancer-free. Right now, that person is 10 or 11 years out cancer-free, and that was her second time getting it, so maybe it worked for her.

Andrew:

What's your attitude about clinical trials?

Denise:

I think they're positive. If you're going to participate in one, you have to be proactive in terms of watching how you're feeling so that you don't put yourself at risk. When I was in one of the trials, I actually was at-risk. I was getting interleukin II, and it was giving me very high temps. I decided that I was never going get better if I didn't get off of that trial. Every day, I'd get the shot, and then a couple of hours later I'd be really sick. Once they stopped, I got better. Be aware of the side effects and take charge if you have to.

Andrew:

Did your family support your participation in trials, with you being the ultimate decision-maker?

Denise:

Oh, I think so. I make my own decisions. I was the one living it. The family just said, "Whatever you want to do, go ahead with it."

Andrew:

Denise, we fast-forward a few years to 2003, when you had a third recurrence - lumps at the center of your chest. Tell us about that.

Denise:

I developed a cough that just didn't seem to go away. I did have a CAT scan, and it showed three little lumps in the area of the mediastinum. They were small, but just enough to be an annoyance. They were not operable, and they were not radiatable, so I thought, "Wow, maybe I don't have a chance. There's no hope." But doctors convinced me to try different treatments. That's when I had Arimidex [anastrozole], and that didn't work. We tried Xeloda [capecitabine], and I developed a reaction - the hand-and-foot syndrome. By the end of 14 days, I had nausea and the blisters and overall malaise. Then we went to the Faslodex [fulvestrant], so that would be '04.

Andrew:

Now, I understand that at some point cancer was discovered to have spread to your liver and lungs.

Denise:

Right, I had radiation pneumonitis, which is similar to like a pneumonia, so I went to see a pulmonologist who said this is treatable. It took at least two months to clear up the pneumonitis. January of 2005, I actually thought that I wasn't going to make it. It's the first time I think in the last 14 years that I've ever felt like I'm not getting better.

The pulmonologist needed a CAT scan to confirm the radiation pneumonitis. When the CAT scan came back, it confirmed the pneumonitis, but at the same time it showed the cancer was fully involved in the liver and I had at least two lesions in the lower lobe of the lung.

Diagnosed in the early 90s, you go for five years or so, then it shows up in your neck, then later it's discovered in your chest, and now at the beginning of 2005, it's shown to be in your liver and in your lungs.

Andrew:

You go back to Dr. [Sheila] Donnelly. What are we going to do about this?

Denise:

She says we have three choices. We could have tried exemestane, and another one was to go to Taxol, which I'd had before. She said, "There's this new thing that just came out called Abraxane, which was a nab paclitaxel. It was delivered in an albumin base, and there was a lot of positiveness about that. I decided to go on the Abraxane. It was to begin in February. I said okay, I'll have it once a week, so I had a port put in, and I started on the 15th.

My tumor marker was as high as about 428 in January. The tumor marker went down after the second treatment of Abraxane, from 428 to 329.

Andrew:

Denise, at the beginning of 2005, with the lung problems you had, the news that your cancer had spread to your liver and your lungs, and now trying a new drug, you must have been feeling pretty down. Then your tumor markers begin to go down, and you were feeling better. It must have been a big change and a lift for you.

Denise:

Oh, it was, it was. In January, I really didn't think I was going to be here at the end of 2005. I figured that's the end because I knew I didn't feel well. I wouldn't say I wasn't depressed about it. It was just the writing's on the wall. I tried the Abraxane, and then every month we do a tumor marker. Last month, my tumor markers were 49.

Andrew:

Beyond this dramatic drop in your tumor marker, you started feeling better and were able to get back to living. Tell us what activities you've been able to do.

Denise:

I have never stopped doing water aerobics. I've been doing that since 1998, after the transplant. I was having such a difficult time breathing, yet I was able to because you can do it at your own pace. It wasn't until March that I started feeling good and noticeably different and able to do golfing. I use a cart, but I still can golf. There was a while that it would be like nine holes, and I was dead. But then I got on Procrit [epoetin], maybe once a month, maybe twice a month, and it just brings your counts up, so you have more energy [Medical editor's note: Procrit boosts the production of red blood cells, therefore fighting anemia.]

Andrew:

You've described this gauntlet that you've run of cancer and recurrence and recurrence and recurrence again, and different therapies. How do you feel today, and how do you feel about the future?

Denise:

I feel fine today. I had Abraxane this morning, and after that you feel a little uneasy or queasy. But it's nothing when you think about it. It's working.

Andrew:

You had had Taxol, and you had had a lot of side effects. But you haven't had that with Abraxane?

Denise:

Yes and no, [I've had] maybe a small amount of bone pain, but I can't tell if it's because of that. About a month ago, I had another CAT scan, and that's when they found it in the bones.

But they can see it healing in the bones.

Andrew:

Denise, what would you say to a woman who may get the news that her breast cancer has recurred and think that's all she wrote? That hasn't at all been the case for you.

Denise:

There are new things coming out, and hopefully this one is going to work for a long time. My experiences have been that you try a treatment, and it works for 10 or 11 months, sometimes only three or four months or sometimes not at all. So you just keep trying another new treatment. Of course, you lose your hair but that's not a big deal. You know, I've lost it three or four times, so what difference does it make? You wear a hat. You wear a wig.

Andrew:

Denise St. Laurent, I applaud you for what you've done in being informed and asking questions and going around to different doctors, and yet still retaining control and being willing to be part of clinical trials. There are a lot of new things that come along so that you can live with cancer and have grandchildren and lead a long life.

This site complies with the HONcode standard for trustworthy health information: verify here.

Advertising Notice

This Site and third parties who place advertisements on this Site may collect and use information about your visits to this Site and other websites in order to provide advertisements about goods and services of interest to you. If you would like to obtain more information about these advertising practices and to make choices about online behavioral advertising, please click here.